Enzyme substrates and inhibitors have high affinities for their enzymes, and usually bind to a few specific sites. The binding of large amphiphiles such as detergents is less specific, and very large amounts may be bound. It is planned to study the extent to which the non-specific binding of high-affinity ligands (principally anionic detergents) by proteins also occurs with oligo peptides and small peptides as well as the amides of simple amino-acids. A new method of detecting such binding - namely, enhancement of the hydrolysis of their primary (amide) and secondary (peptide) bonds by anions of high affinity for proteins will be used. The mechanism of this powerful enhancement will also be subjected to study for its possible relevance to the action of proteolytic enzymes. The relevance of the propsed research to health-related objectives derives from the fact that many metabolites, including the water-insoluble lipids and steroids, which chemically resemble detergents, circulate in the organism, and may even participate in metabollsm, only as protein-complexes. The question then arises as to whether they are also complexed, although to a lesser extent, by oligo peptides or even by very small peptides (such as vasopressin) which circulate in the blood. The ligands of interest would include, in addition to detergents, lipids and steroids, a selection of toxins, medications, and drugs. As outlined in the proposal a systematic survey will be made of the formation of complexes by each of a group of amino-acids, peptides, and oligo peptides (both homo- and heteropolymers) with a small number of anionic detergents which have demonstrated a high non-specific binding to proteins, and which also greatly enhance the rats of hydrolysis of the latter in acid solutions. A wide range of concentrations, temperatures, and ionic strengths will be used. The results may help furnish a basis for design of ligands for possible pharmacological use. They may also contribute to our understanding of the action of proteolytic enzymes.